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11.
Yuji Nakamura Teppei Fujimoto Yasuyuki Ogawa Hidenori Namiki Sayaka Suzuki Masayoshi Asano Chie Sugita Akiyoshi Mochizuki Shojiro Miyazaki Kazuhiko Tamaki Yoko Nagai Shin-ichi Inoue Takahiro Nagayama Mikio Kato Katsuyoshi Chiba Kiyoshi Takasuna Takahide Nishi 《Bioorganic & medicinal chemistry》2013,21(11):3175-3196
With the aim to address an undesired cardiac issue observed with our related compound in the recently disclosed novel series of renin inhibitors, further chemical modifications of this series were performed. Extensive structure–activity relationships studies as well as in vivo cardiac studies using the electrophysiology rat model led to the discovery of clinical candidate trans-adamantan-1-ol analogue 56 (DS-8108b) as a potent renin inhibitor with reduced potential cardiac risk. Oral administration of single doses of 3 and 10 mg/kg of 56 in cynomolgus monkeys pre-treated with furosemide led to significant reduction of mean arterial blood pressure for more than 12 h. 相似文献
12.
Sayaka Moriwaki Hiroki Murakami Nobuyuki Takahashi Taku Uemura Keiko Taketani Shohei Hoshino 《Bioscience, biotechnology, and biochemistry》2013,77(7):1231-1236
Yamogenin is a diastereomer of diosgenin, which we have identified as the compound responsible for the anti-hyperlipidemic effect of fenugreek. Here, we examined the effects of yamogenin on the accumulation of triacylglyceride (TG) in hepatocytes, because yamogenin is also contained in fenugreek. It was demonstrated that yamogenin also inhibited TG accumulation in HepG2 hepatocytes and suppressed the mRNA expression of fatty acid synthesis-related genes such as fatty acid synthase and sterol response element-binding protein-1c. Indeed, yamogenin also antagonized the activation of the liver X receptor (LXR) in luciferase ligand assay similar to diosgenin. However, yamogenin could not exert such effects in the presence of T0901713, a potent agonist of LXR. These findings indicate that the effects of yamogenin on TG accumulation would be weaker than those of diosgenin, suggesting that the structural difference between yamogenin and diosgenin would be important for the inhibition of LXR activation. 相似文献
13.
Ken Fukami Kiyoshi Kawai Sayaka Takeuchi Yoshito Harada Yoshio Hagura 《Food biophysics》2016,11(4):410-416
To understand the fundamental physical properties of calcium maltobionate (MBCa), its water sorption isotherm, glass transition temperature (T g), and viscosity (η) were investigated and compared with those of maltobionic acid (MBH) and maltose. Although amorphous maltose crystalized at water activity (a w) higher than 0.43, MBCa and MBH maintained an amorphous state over the whole a w range. In addition, MBCa had a higher T g and greater resistance to water plasticizing than MBH and maltose. These properties of MBCa likely originate from the strong interaction between MBCa and water induced by electrostatic interactions. Moreover, the effects of temperature and water content on η of an aqueous MBCa solution were evaluated, and its behavior was described using a semi-empirical approach based on a combination of T g extrapolated by the Gordon-Taylor equation and a non-Arrhenius formula known as the Vogel–Fulcher–Tammann equation. This result will be useful for understating the effect of MBCa addition on the solution’s properties. 相似文献
14.
Sayaka Nakashima Zhe Liu Yuya Yamaguchi Shunya Saiki Shintaro Munemasa Toshiyuki Nakamura Yoshiyuki Murata Yoshimasa Nakamura 《Biochemistry and Biophysics Reports》2016
3,4-Dihydroxyphenylacetic acid (DOPAC) is one of the colonic microflora-produced catabolites of quercetin 4′-glucoside (Q4′G). Although the interaction of DOPAC with cellular proteins might be involved in its biological activity, the actual proteins have not yet been identified. In this study, we developed a novel tag-free DOPAC probe to label the targeted proteins by the copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) and verified its efficacy. Various labeled proteins were detected by the DOPAC probe with the azide labeled biotin and a horseradish peroxidase (HRP)-streptavidin complex. Furthermore, a pulldown assay identified Keap1 and aryl hydrocarbon receptor (AhR) as the target proteins for the phase 2 enzyme up-regulation. 相似文献
15.
Hirotake Abe Haruka Wada Muhammad Baghdadi Sayaka Nakanishi Yuu Usui Takahiro Tsuchikawa Toshiaki Shichinohe Satoshi Hirano Ken-ichiro Seino 《Human cell》2016,29(2):58-66
Cancer vaccines serve as a promising clinical immunotherapeutic strategy that help to trigger an effective and specific antitumor immune response compared to conventional therapies. However, poor immunogenicity of tumor cells remains a major obstacle for clinical application, and developing new methods to modify the immunogenicity of tumor cells may help to improve the clinical outcome of cancer vaccines. 4T1 mouse breast cancer cell line has been known as poorly immunogenic and highly metastatic cell line. Using this model, we identified a sub cell line of 4T1—designated as 4T1-Sapporo (4T1-S)—which shows immunogenic properties when used as a vaccine against the same line. In 4T1-S-vaccinated mice, subcutaneous injection of 4T1-S resulted in an antitumor inflammatory response represented by significant enlargement of draining lymph nodes, accompanied with increased frequencies of activated CD8 T cells and a subpopulation of myeloid cells. Additionally, 4T1-S vaccine was ineffective to induce tumor rejection in nude mice, which importantly indicate that 4T1-S vaccine rely on T cell response to induce tumor rejection. Further analysis to identify mechanisms that control tumor immunogenicity in this model may help to develop new methods for improving the efficacies of clinical cancer vaccines. 相似文献
16.
Curcumin glucosyltransferase (CaUGT2) isolated from cell cultures of Catharanthus roseus exhibits unique substrate specificity. To identify amino acids involved in substrate recognition and catalytic activity of CaUGT2, a combination of domain swapping and site-directed mutagenesis was carried out. Exchange of the PSPG-box of CaUGT2 with that of NtGT1b (a phenolic glucosyltransferase from tobacco) led to complete loss of enzyme activity in the resulting recombinant protein. However, replacement of Arg378 of the NtGT1b PSPG-box with cysteine, the corresponding amino acid in CaUGT2, restored the catalytic activity of the chimeric enzyme. Further site-directed mutagenesis revealed that the size of the amino acid side-chain in that particular site is critical to the catalytic activity of CaUGT2. 相似文献
17.
Kimata-Ariga Y Kurisu G Kusunoki M Aoki S Sato D Kobayashi T Kita K Horii T Hase T 《Journal of biochemistry》2007,141(3):421-428
The human malaria parasite (Plasmodium falciparum) possesses a plastid-derived organelle called the apicoplast, which is believed to employ metabolisms crucial for the parasite's survival. We cloned and studied the biochemical properties of plant-type ferredoxin (Fd) and Fd-NADP+ reductase (FNR), a redox system that potentially supplies reducing power to Fd-dependent metabolic pathways in malaria parasite apicoplasts. The recombinant P. falciparum Fd and FNR proteins were produced by synthetic genes with altered codon usages preferred in Escherichia coli. The redox potential of the Fd was shown to be considerably more positive than those of leaf-type and root-type Fds from plants, which is favourable for a presumed direction of electron flow from catabolically generated NADPH to Fd in the apicoplast. The backbone structure of P. falciparum Fd, as solved by X-ray crystallography, closely resembles those of Fds from plants, and the surface-charge distribution shows several acidic regions in common with plant Fds and some basic regions unique to this Fd. P. falciparum FNR was able to transfer electrons selectively to P. falciparum Fd in a reconstituted system of NADPH-dependent cytochrome c reduction. These results indicate that an NADPH-FNR-Fd cascade is operative in the apicoplast of human malaria parasites. 相似文献
18.
Akihiro Kuno Yoshihisa Ikeda Shinya Ayabe Kanako Kato Kotaro Sakamoto Sayaka R. Suzuki Kento Morimoto Arata Wakimoto Natsuki Mikami Miyuki Ishida Natsumi Iki Yuko Hamada Megumi Takemura Yoko Daitoku Yoko Tanimoto Tra Thi Huong Dinh Kazuya Murata Michito Hamada Masafumi Muratani Atsushi Yoshiki Fumihiro Sugiyama Satoru Takahashi Seiya Mizuno 《PLoS biology》2022,20(1)
Genome editing can introduce designed mutations into a target genomic site. Recent research has revealed that it can also induce various unintended events such as structural variations, small indels, and substitutions at, and in some cases, away from the target site. These rearrangements may result in confounding phenotypes in biomedical research samples and cause a concern in clinical or agricultural applications. However, current genotyping methods do not allow a comprehensive analysis of diverse mutations for phasing and mosaic variant detection. Here, we developed a genotyping method with an on-target site analysis software named Determine Allele mutations and Judge Intended genotype by Nanopore sequencer (DAJIN) that can automatically identify and classify both intended and unintended diverse mutations, including point mutations, deletions, inversions, and cis double knock-in at single-nucleotide resolution. Our approach with DAJIN can handle approximately 100 samples under different editing conditions in a single run. With its high versatility, scalability, and convenience, DAJIN-assisted multiplex genotyping may become a new standard for validating genome editing outcomes.Genome editing can introduce designed mutations into a target genomic site, but also into unintended off-target sites. DAJIN, a novel nanopore sequencing data analysis tool, identifies and quantifies allele numbers and their mutation patterns, reporting consensus sequences and visualizing mutations in alleles at single-nucleotide resolution. 相似文献
19.
Yamada Y Hosono R Lisdyanti P Widyastuti Y Saono S Uchimura T Komagata K 《The Journal of General and Applied Microbiology》1999,45(1):23-28
Sixty-four strains of acetic acid bacteria were isolated from Indonesian sources such as fruits, flowers, and fermented foods by the enrichment culture at pH 3.5. Forty-five strains were routinely identified as Acetobacter strains because of their oxidation of acetate and lactate to carbon dioxide and water and their Q-9 isoprenolog, corresponding to 70% of all the 64 acetic acid bacteria isolated. Eight isolates were identified as Gluconacetobacter strains because of their oxidation of acetate and lactate and their Q-10 isoprenolog, occupying 13% of all the isolates. The remaining 11 isolates, accommodated in the genus Gluconobacter because of no oxidation of acetate and lactate and because of their Q-10 isoprenolog, accounted for 17% of all the isolates. They were divided into two groups based on DNA base compositions. One comprised the seven isolates, which had high G1C contents of DNA ranging from 60.3 to 63.5 mol% and of which DNAs hybridized with that of the type strain of Gluconobacter oxydans at values of 64-94% of DNA relatedness. The other comprised the remaining four isolates, which had low G+C contents of DNA ranging from 57.5 to 57.7 mol% and of which DNAs hybridized with that of the type strain of Gluconobacter frateurii at values of 63-77% of DNA relatedness. The high values of DNA relatedness, 84 to 96%, were obtained between the type strains of Gluconobacter cerinus and Gluconobacter asaii. 相似文献
20.
Spiraea thunbergii Sieb. was found to contain 1-O-cis-cinnamoyl-beta-D-glucopyranose and 6-O-(4'-hydroxy-2'-methylene-butyroyl)-1-O-cis-cinnamoyl-beta-D-glucopyranose as major plant growth inhibitory constituents along with related compounds of lower phytotoxicity including 6-O-(trans-cinnamoyl)-1-O-(4"-hydroxy-3"-methyl-furan-2"-one)-beta-D-glucopyranose, 6-O-(4'-hydroxy-2'-methylene-butyroyl)-1-O-trans-cinnamoyl-beta-D-glucopyranose, and 1-O-trans-cinnamoyl-beta-D-glucopyranose. The former three compounds were cinnamoyl glucosides. 相似文献